16-1788835-C-G

Variant names:

• chr16-1788835-C-G
• rs1065656
• NM_012225.4:c.*121C>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001284502.2(NUBP2):​c.491C>G​(p.Pro164Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.684 in 1,286,368 control chromosomes in the GnomAD database, including 303,674 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/5 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (37770 hom., cov: 34)
  • Exomes 𝑓: 0.68 (265904 hom.)
• Consequence: NUBP2 NM_001284502.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.04

Genes affected

NUBP2 (HGNC:8042): (NUBP iron-sulfur cluster assembly factor 2, cytosolic) This gene encodes an adenosine triphosphate (ATP) and metal-binding protein that is required for the assembly of cyotosolic iron-sulfur proteins. The encoded protein functions in a heterotetramer with nucleotide-binding protein 1 (NUBP1). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2013]

SPSB3 (HGNC:30629): (splA/ryanodine receptor domain and SOCS box containing 3) Predicted to be involved in proteasome-mediated ubiquitin-dependent protein catabolic process. Predicted to be located in cytosol. Predicted to be part of SCF ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.773 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NUBP2	NM_012225.4	c.*121C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000262302.14	NP_036357.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NUBP2	ENST00000262302.14	c.*121C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_012225.4	ENSP00000262302.9

Frequencies

GnomAD3 genomes AF: 0.702 AC: 106667 AN: 152022 Hom.: 37741 Cov.: 34

Gnomad AFR AF: 0.781

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.739

Gnomad EAS AF: 0.561

Gnomad SAS AF: 0.586

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.714

GnomAD4 exome AF: 0.682 AC: 773558 AN: 1134228 Hom.: 265904 Cov.: 15 AF XY: 0.678 AC XY: 375219 AN XY: 553424

Gnomad4 AFR exome AF: 0.787

Gnomad4 AMR exome AF: 0.708

Gnomad4 ASJ exome AF: 0.728

Gnomad4 EAS exome AF: 0.485

Gnomad4 SAS exome AF: 0.564

Gnomad4 FIN exome AF: 0.579

Gnomad4 NFE exome AF: 0.696

Gnomad4 OTH exome AF: 0.685

GnomAD4 genome AF: 0.702 AC: 106748 AN: 152140 Hom.: 37770 Cov.: 34 AF XY: 0.692 AC XY: 51498 AN XY: 74372

Gnomad4 AFR AF: 0.781

Gnomad4 AMR AF: 0.699

Gnomad4 ASJ AF: 0.739

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.584

Gnomad4 FIN AF: 0.563

Gnomad4 NFE AF: 0.690

Gnomad4 OTH AF: 0.716

Alfa AF: 0.579 Hom.: 1532

Bravo AF: 0.722

Asia WGS AF: 0.574 AC: 1999 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.34
DANN	Benign	0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1065656; hg19: chr16-1838836;